1. Field
Provided is an anti-c-Met/anti-Ang2 bispecific antibody, a composition including the anti-c-Met/anti-Ang2 bispecific antibody, and a method of preventing and/or treating a cancer in a subject including administering the anti-c-Met/anti-Ang2 bispecific antibody to the subject.
2. Description of the Related Art
Angiopoietin2 (Ang2) is an antagonistic ligand of receptor Tie2 present in vascular endothelial cell (Nat Rev Mol Cell Biol. 2009 March; 10(3):165-77), and competes with Angiopoietin1 (Ang1) which is an agonist of Tie2 for binding to Tie2, thereby inhibiting the signal transduction by Tie2 (Science. 1997 Jul. 4; 277(5322):55-60). Therefore, Ang2 inhibits Ang1-Tie2 signal transduction for maintaining stability of vascular endothelial cells, leading to stimulation of angiogenesis by dynamic rearrangement of blood vessels (Science. 1997 Jul. 4; 277(5322):48-50). It is known from many preclinical studies that since the angiogenesis process is essential to cancer growth, the inhibition of the Tie2-dependent Ang2 functions can lead to the inhibition of angiogenesis, thereby preventing additional growth of cancer (J Natl. Cancer Inst. 2012 Mar. 21; 104(6):461-75). There have been many attempts to prevent cancer using an Ang2 specific antibody by many global pharmaceutical companies, such as Regeneron, Astrazeneca, Amgen, and the like. However, the recent studies have suggested that when a cancer cell is treated with an angiogenesis inhibitor, a mechanism for avoiding the sudden oxygen deficiency condition is activated in the cancer cell, which can stimulate cancer metastasis (Nat. Rev. Clin. Oncol. 2011 Mar. 1; 8(4):210-21) even in the absence of angiogenesis. Therefore, to avoid such serious side effects of angiogenesis inhibitors, it is necessary to inhibit functions of cancer metastasis-related proteins as well.
c-Met is a representative receptor tyrosine kinase (RTK) present on certain cell surfaces. c-Met binds to its ligand, Hepatocyte Growth Factor/Scattering Factor (HGF/SF), to promote intracellular signal transduction, thereby stimulating cell growth, and it is overexpressed in many cancer cells, thereby widely relating to cancer occurrence, cancer metastasis, cancer cell migration, cancer cell invasion, and angiogenesis. In addition, c-Met is a representative early protein of cancer metastasis, because c-Met signaling through HGF/SF weakens cell-cell contact in almost all types of epithelial tumors, leading to scattering. (Nat Rev Cancer. 2012 Jan. 24; 12(2):89-103). In particular, hypoxia-response elements are present at the upstream of c-Met gene, and the expression of the gene is increased under oxygen deficient conditions (Oral Oncol. 2006 July; 42(6):593-8).
Therefore, simultaneous inhibition of Ang2 and c-Met may lead to more effective inhibition of cancer cell growth and metastasis, and thus, it is needed to develop a drug that simultaneously targets both Ang2 and c-Met.